MY CONFLICTS OF INTEREST ARE Grant support, Siemens Medical Solutions Consultant, GlaxoSmithKline.

MY CONFLICTSOF INTEREST ARE

Grant support, Siemens Medical Solutions Consultant, GlaxoSmithKline

Advanced Angioplasty 2007

MRI in Ischemic Heart Disease

Stefan Neubauer, MD FRCP FACCProfessor of Cardiovascular Medicine

Department of Cardiovascular MedicineUniversity of Oxford

John Radcliffe HospitalOxford UK

Imaging in Ischemic Heart DiseaseImaging in Ischemic Heart Disease

• Chest X-ray

• Echocardiography

• Nuclear scintigraphy

• Catheterisation

• Chest X-ray

• Echocardiography

• Nuclear scintigraphy

• Catheterisation

Resolution

Information Radiation

Invasiveness• Cardiac Cardiac MRMRII

The Comprehensive Cardiac MR (CMR) ExaminationThe Comprehensive Cardiac MR (CMR) Examination

• Cardiac and great vessel anatomy

• Cardiac volumes and mass

• Global and regional contractile function

• Regional myocardial tissue perfusion

• Regional myocardial tissue characteristics:

Viability, oedema, inflammation, fibrosis, metabolism

• Coronary artery lumen, wall anatomy, blood flow

Goal: <30 min acquisition, <10 min post-processingGoal: <30 min acquisition, <10 min post-processing

1. What CMR has to offer

2. CMR research in PCI

Comprehensive CMR Study

• High resolution anatomy

• Global / regional function

• Regional perfusion

• Viability/Oedema/Fibrosis

• Coronary Angiography

Horizontal long axis Vertical long axis

Cardiac Function: True-FISP MRI

Jane Francis, MR technologist,

University of Oxford Centre for Clinical MR Research

Short axis Stack of short axes

+10mm +20mm +30mm +40mm

+50mm +60mm +70mm +80mm +90mm

Base

Apex

Simpson’s Rule

HLA cinePre-vs. post-surgery MRI

pre postNorm

EDV (ml) 1423 167 77-195

EF (%) 3 54 56-78

Selvanayagam J et al, Circulation 2003

Tissue Phase Mapping

Regional Tissue Contractility

3D Velocities: Radial, circumferential, longitudinal

Petersen S et al, Radiology 2005

Dobutamine-Stress MR: 4-Chamber

rest 20 µg

40 µg30 µg

Nagel E et al, Circulation 1999

Influence of image quality

0

10

20

30

40

50

60

70

80

90

100

good / very good moderate

sensitivity (DSE)

specificity (DSE)

sensitivity (DSMR)

specificity (DSMR)

E. Nagel, Z Kardiol 1999



• Regional perfusion - GdDTPA




<10s

PerfusioPerfusionn

10-20 min

InfarctInfarct

[Gd]

time

“First pass” study: Time-intensity curves

Normal

Ischemia/Infarct

LV Blood pool

Myocardial Perfusion - Quantification

Wilke N et al. MRM 1993

• Qualitative (eyeballing)

• Semi-quantification (upslope)

→ perfusion reserve

• Absolute quantification (ml/min x g)

Rest and stress perfusion(i.v. Adenosine 140g/kg x min)

Regional Myocardial Perfusion

• n=84

• Prevalence of CAD 51%

• Sensitivity 88%

• Specificity 90%

• Diagnostic accuracy 89%

Nagel E el al. Circulation 2003

Wolff SD et al, Circulation 2004Giang TH et al, Eur Heart J 2004

MR IMPACT II (Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary artery disease Trial)

A phase III multicenter, multivendor trial comparing perfusion cardiac magnetic resonance versus

single photon emission computed tomography for the detection of coronary artery disease.

J. Schwitter, 1 C. Wacker, 2 N. Wilke, 3 N. Al-Saadi, 4 N. Hoebel, 5 T. Simor 6

1 Zurich, Switzerland, 2 Würzburg, Germany, 3 Gainesville/Jacksonville, US 4 Berlin Germany, 5 Munich, Germany, GEHC, 6 Pecs, Hungary

• 33 centres, 1.5 Tesla, 465 patients• Patients with chest pain undergoing coronary angiography• CAD defined as >50% diameter stenosis in at least one vessel with at

least 2mm diameter

CardioVascularMR Center Zurich

0

0.25

0.5

0.75

1

0 0.25 0.5 0.75 1

1-Specificity

MR-IMPACT II 33 Centers – Multivendor: Dose 0.075 mmol/kg Gd-DTPA-BMA

*

Se

ns

itiv

ity


SPECT all n=465 AUC: 0.65±0.03 P=0.0004

Perfusion-CMR n=465 AUC: 0.75±0.02

gated-SPECT n=277 AUC: 0.69±0.03 P=0.018ungated-SPECT n=188 AUC: 0.63±0.04 P=0.023 P=ns vs Gated

0

0.25

0.5

0.75

1

0 0.25 0.5 0.75 1

1-Specificity

MR-IMPACT II - MVD33 Centers – Multivendor: Dose 0.075 mmol/kg Gd-DTPA-BMA

Se

ns

itiv

ity


SPECT all n=339 AUC: 0.72±0.03 P=0.003

Perfusion-CMR n=339 AUC: 0.80±0.03

gated-SPECT n=188 AUC: 0.75±0.04 P=0.040ungated-SPECT n=140 AUC: 0.69±0.05 P=0.049 P=ns vs Gated

1-3 VD SPECT

MR-IMPACT IIIt is the largest multicenter MR/SPECT trial performed so far using 99mTc-tracers and ECG-gating (33 centers, 465 patients)It shows:

Perfusion-CMR (at 0.075 mmol/kg Gd-DTPA- BMA) is superior to SPECT for the detection of coronary artery disease

Perfusion-CMR is a short and safe test, is sensitive and specific, and can be recommended as an alternative for SPECT imaging in experienced centers


Comparison of 3T vs. 1.5T CMR Comparison of 3T vs. 1.5T CMR PerfusionPerfusion3T Stress3T Stress 1.5T Stress1.5T Stress

• 61 patients (age 64±8 years)61 patients (age 64±8 years)

• Referred for diagnostic CA for Referred for diagnostic CA for investigation ofinvestigation of exertional CP exertional CP

• Stress/rest perfusion CMR at Stress/rest perfusion CMR at both 1.5T both 1.5T (Sonata) (Sonata) and 3T and 3T (Trio) (Trio) on same dayon same day

1.00.80.60.40.20

1 - Specificity

1.0

0.8

0.6

0.4

0.2

0

Se

ns

itiv

ity

3 T AUC: 0.89±0.05

1.5 T AUC: 0.70±0.08

p < 0.05

1.00.80.60.40.20

1 - Specificity

1.0

0.8

0.6

0.4

0.2

0

Se

ns

itiv

ity

3 T AUC: 0.89±0.05

1.5 T AUC: 0.70±0.08

p < 0.05

1.00.80.60.40.20

1 - Specificity

1.0

0.8

0.6

0.4

0.2

0

Se

ns

itiv

ity

3 T AUC: 0.95±0.03

1.5 T AUC: 0.82±0.06

p < 0.05

1.00.80.60.40.20

1 - Specificity

1.0

0.8

0.6

0.4

0.2

0

Se

ns

itiv

ity

3 T AUC: 0.95±0.03

1.5 T AUC: 0.82±0.06

p < 0.05

MVDMVD SVDSVD

3T provided a significant 3T provided a significant increase in SNR (17±6 vs. increase in SNR (17±6 vs. 11±2; p<0.01) compared to 11±2; p<0.01) compared to 1.5T1.5T

Cheng A et al, JACC in pressCheng A et al, JACC in press

Delayed Enhancement MRI

• 10 – 20 min post Gd DTPA

• Inversion recovery FLASH or True-FISP

• “Bright is dead”

• Normal, stunned, hibernating

myocardium is dark

Kim R et al, Circulation 1999

Kim R et al, NEJM 2001

Delayed Enhancement MRI

In vivo infarct imaging

LV Function: cine MRILV Function: cine MRI Myocardial Viability: Myocardial Viability: DE-MRIDE-MRI

Superior to SPECT for the Superior to SPECT for the detection of sub-endocardial detection of sub-endocardial infarctioninfarctionWagner et al Lancet 361:378Wagner et al Lancet 361:378

Example: Acute Antero-Septal Infarction

Relationship between transmural extent of HE before bypass Relationship between transmural extent of HE before bypass surgery and likelihood of increased contractility after surgerysurgery and likelihood of increased contractility after surgery

Transmural Extent of Hyperenhancement (%)

Imp

rove

d c

on

trac

tili

ty (

%)

0

20

40

60

80

01-25

26-5051-75

76-100

100

(156

/190

)

(156

/190

)(1

10 /1

72)

(110

/172

)(8

0/16

2)

(80/

162)

(16/

63)

(16/

63)

(1/ 2

5)

(1/ 2

5)

All Dysfunctional Segments

Selvanayagam J et al Selvanayagam J et al Circulation 2004Circulation 2004

Example: Viable vs. non-viable myocardium

Baseline Cine

Del. Enhancement

6 Months Cine

Delayed Enhancement Phenomenon

Acute Myocarditis HCM: Fibrosis

Not specific for ischemic injury

M. Friedrich et al S. Petersen et al McCrohon et al Circulation 2003

DCM: Fibrosis

Imaging of Myocardial Oedema

Aletras et al Circulation 2006

Salvaged myocardium = Area at risk (T2w)– Area of necrosis (DE)

90 min occlusionreperfusionMicrospheres: AARTTC staining: AON

MR Coronary Angiography:Fundamental challenges

• Small structures (1-4mm diameter)

• Need 3 D resolution

• Move rapidly with cardiac cycle

and respiration (RCA by ~ 10cm)

Spatial resolution Temporal resolution

Cardiac cath 0.3 x 0.3 mm 8 ms (shutter speed)

CT Coronary Angiography

Spatial resolution Temporal resolution0.4 x 0.4 x 0.4 mm 120 ms

Achenbach S,Erlangen University

MR Coronary Angiography

Spatial resolution Temporal resolution0.6 x 0.6 x 0.6 mm minutes (navigator)

Sakuma H,Matsusaka Central Hospital, Mie, Japan

CMR research in patients undergoing PCI

CMR: New level of understanding of the interrelations amongst coronary stenosis, myocardial blood flow, function and irreversible injury

1. Use of CMR in monitoring injury from revascularisation procedures

2. Blood flow in

hibernating myocardium

With A. Banning, K. Channon, J. Selvanayagam

Use of CMR in monitoring injury from revascularisation procedures

Questions Occurrence and location of peri-procedural myocardial necrosis in complex PCI?

Relationship between magnitude of troponin rise to the volume of myocardial

tissue loss?

Mechanisms of irreversible myocardial tissue injury?

New HE-8.5g; Trop I 4.8New HE-8.5g; Trop I 4.8

48 consecutive patients undergoing complex PCI48 consecutive patients undergoing complex PCIall received aspirin, clopidogrel and abciximaball received aspirin, clopidogrel and abciximab

24hr Pre and 24 hr Post PCI MRI; pre and 24 hr troponin I24hr Pre and 24 hr Post PCI MRI; pre and 24 hr troponin I

Selvanayagam JB et al, Circulation 2005Selvanayagam JB et al, Circulation 2005

Irreversible myocardial injury

New HyperenhancementNew Hyperenhancement• 14/48 14/48 (29%)(29%) patientspatients

4

8

n = 14n = 14 n = 48n = 48

5% of LV 5% of LV MassMass

1.7 % of LV 1.7 % of LV MassMass

New

Hyp

eren

han

cem

ent

(gra

ms)

New

Hyp

eren

han

cem

ent

(gra

ms)

Selvanayagam JB et alSelvanayagam JB et al

Circulation 2005Circulation 2005

Correlation of cTnI rise with new myocardial hyperenhancement

33

88

1313

1818N

ew H

yper

enh

ance

men

t (g

ram

s)N

ew H

yper

enh

ance

men

t (g

ram

s)

22 55 88

Troponin rise at 24 hrs (Troponin rise at 24 hrs (ųųg/L)g/L)

r= 0.84r= 0.84

p<0.001p<0.001

00

n = 48n = 48


Relationship Between Plaque Volume and Occurrence and Location of Peri-Procedural Myocardial Necrosis Following PCI

New HENew HE• 15/64 (23%)15/64 (23%) vesselsvessels

2

4

n = 8n = 8 n = 7n = 7New

New

Hyp

eren

han

cem

ent

(gra

ms)

Hyp

eren

han

cem

ent

(gra

ms)

p p = 0.6= 0.6

DistalDistal AdjacentAdjacent

Porto I et al, Circulation 2006 Porto I et al, Circulation 2006

Example: Pre PCI

AngiogramAngiogram IVUSIVUS DE-CMR DE-CMR


Example: Post PCI

AngiogramAngiogram IVUSIVUS DE-CMR DE-CMR


Plaque Volume vs. Location of Peri-Procedural Myocardial Necrosis

}}** }}**}}** }}**

**p<0.001p<0.001

No HENo HE DistalDistal AdjacentAdjacent No HENo HE DistalDistal AdjacentAdjacent


Blood flow in hibernating myocardium

Impairment in perfusion reserve is well recognized in myocardium supplied by significantly diseased coronary arteries (CAD)

However, it is unknown whether resting blood flow is abnormal in such myocardium

Studies to date mainly using PET have produced conflicting results

Background

Methods

27 patients undergoing percutaneous coronary intervention (PCI)

one/ two vessel CAD (>85% stenosis by QCA) at least one dysfunctional segment

Cine & Cine & Rest Rest

Perfusion Perfusion DE CMRDE CMR

PCIPCICine Cine

Rest PerfusionRest Perfusion

DE CMRDE CMR

Cine Cine CMRCMR

9 months9 months24h24h 24h24h

CMR Perfusion: Absolute quantification of blood flow

95% stenosis of proximal LAD95% stenosis of proximal LAD


Blood flow in hibernating segments

• No delayed enhancement

• Significant recovery of function at 9 months


Segments with

MeanMeancorrectedcorrected

MBFMBFpre-PCIpre-PCI

** ****

******

p < 0.001p < 0.001p < 0.0001p < 0.0001

NSNS

Selvanayagam JB et al Circulation 2005Selvanayagam JB et al Circulation 2005

Relationship between transmural scar and baseline/post- PCI blood flow

• Troponin elevation 24 hr post PCI represents new Troponin elevation 24 hr post PCI represents new myocardial injurymyocardial injury

• Both impairment of side branches and distal embolisation of Both impairment of side branches and distal embolisation of plaque material contribute to myocardial necrosis during PCIplaque material contribute to myocardial necrosis during PCI

• Resting myocardial blood flow is reduced in hibernating Resting myocardial blood flow is reduced in hibernating myocardiummyocardium

Summary of Oxford PCI research studies

Clinical CMR Techniques on the Horizon• Regional strain (tissue phase mapping)

• Non-contrast perfusion (ASL)

• Oxygenation (BOLD)

• 23Na-Imaging

• Metabolism (MRS)

• 7 Tesla

• Molecular ImagingSelvanayagam J et al, works in progress

Robson M et al Works in Progress

PCr

- - -ATP

2,3-DPG

PDE

5 0 -5 -10 -15 -20 ppm

Non-invasiveimaging tool

MRI in Ischemic Heart Disease

Multi-parametricphenotyping

Clinical studies of patients with IHD

DiagnosticCardiology

Acknowledgments

OCMRJoseph Selvanayagam, Ranjit Arnold, Adrian Cheng

CollaboratorsAdrian Banning

Keith Channon

Michael Jerosch-Herold

Italo Porto

William van Gaal

FundingBritish Heart FoundationMedical Research CouncilThe Wellcome TrustSiemens Medical Solutions

Myocardial Viability: Clinical Relevance

Schelbert H et al,Seminars in Nuclear Medicine 2002

Pagano et al, J Thorac Cardiovasc Surgery 1998

Myocardial ViabilityThe Clinical Problem:

Akinetic myocardium,supplied by stenosed coronary artery

Viable= Stunning, Hibernation

Non-viable= Scar

Revascularisation(PTCA, CABG)

No Revascularisation

Methods The diagnostic coronary angiogram was used to define affected

myocardial segments

Wall motion was assessed visually:normal 1; hypokinetic 2; akinetic 3; dyskinetic 4.

In each slice, MBF was determined for 8 myocardial sectors in ml/min/g by deconvolution of signal intensity curves with an arterial input function measured in the LV blood pool

Jerosch-Herold, M. et. al JMRI 2004

ResultsCoronary lesion severity was 80-95% stenosis by quantitative coronary angiography

Mean MBF normalized by rate pressure product (‘corrected MBF’) was 1.2+/-0.3 in segments without significant coronary stenosis and 0.7 +/-0.2 in segments with coronary stenosis pre PCI (z=23.9, p<0.001)

Early post procedure, the MBF was 1.2+/-0.2 in revascularised segments, and 1.3+/-0.2 in non-diseased segments

Methods

Prep

3 MinAdeno

0.14mg//kg/min

LEImaging

BH BH

25‘

MR Study and Monitoring:


–2 to 0hVit Signs

12-ECG

1-1.5 hVit S

12-ECG

24 hVit SPhys

12-ECGLabAE

1 hVit S

12-ECG

- 36h to 0 hHistory

Phys. ExamSymptomsPreg TestBlood Lab

4 weeks: QCA

4 weeks: SPECT

4 weeks: QCA

4 weeks: SPECT

0.075 mmol/kg Gd-DTPA-BMA

0.075 mmol/kg Gd-DTPA-BMA

Vital signs (HR, BP, O2 sat, etc)

~1.5h

72 hAE10‘

SPECT stress perfusion

99mTc: Sestamibi, Teboroxime, Tetrofosmin

SPECT Study: gated-SPECT (ungated-SPECT allowed if clinical routine)

Multi-Vendor1-Day Protocol permitted

Preparation

Adeno 0.14mg/ /kg/min

Stress Rest


Methods

Identical to stress perfusion

99mTc: Sestamibi, Teboroxime, Tetrofosmin

• Physics complex

• Nuclear spin

• External magnetic field

• RF waves -> FID

MR (NMR) - Nuclear Magnetic ResonanceMR (NMR) - Nuclear Magnetic Resonance

• Magnetic field gradient

• MR image contrast: - Spin density

- Relaxation (T1, T2)

- Flow

- Pulse sequence

Nature 1973; 242:190-191

MY CONFLICTS OF INTEREST ARE Grant support, Siemens Medical Solutions Consultant, GlaxoSmithKline.

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Transcript of MY CONFLICTS OF INTEREST ARE Grant support, Siemens Medical Solutions Consultant, GlaxoSmithKline.